MADISON, WIS-- Long-term use of oral corticosteroids impairs growth in children with cystic fibrosis (CF). In boys, this impairment persists for up to seven years after the drug has been discontinued and results in shorter stature and lower weight in adulthood, according to Hui-Chuan Lai, PhD, RD, and colleagues at the University of Wisconsin School of Medicine in Madison.[1]

"Our main finding was that long-term oral prednisone caused persistent growth retardation in boys who have CF but not in girls, and that growth retardation was more severe in boys who were younger when they began taking prednisone," Dr. Lai told RESPIRATORY REVIEWS. The researchers concluded, therefore, that prolonged prednisone therapy should not be used in children who have CF.

"We found that the growth inhibition persisted after the drug was discontinued," Dr. Lai said. "This has not been shown before and has important clinical implications. We suspected that growth inhibition would be present, but we were surprised that it continued for six to seven years after prednisone was discontinued."

Glucocorticoid treatment is used to reduce inflammation and improve lung function in some CF patients. A multicenter clinical trial conducted between 1986 and 1991 had evaluated the use of alternate-day oral prednisone (1 mg/kg or 2 mg/kg) in 224 children age 6 to 14 years to determine whether such treatment could improve pulmonary function.[2] The trial was discontinued in 1991, owing to a higher-than-expected number of adverse events. Dr. Lai's group retrospectively evaluated the growth patterns of these children during the trial and then reevaluated them in 1997, by which time 68% of the children were 18 years of age or older.

Growth declined throughout prednisone treatment, but catch-up growth began two years after prednisone was discontinued. However, even after six years, boys who had been treated with prednisone remained significantly shorter than boys with CF who received placebo (Figure 1).

"The mean heights for boys 18 years of age or older were 4 cm less in the prednisone groups than in the placebo group, an equivalent of 13 percentile points," Dr. Lai reported. Prednisone treatment did produce substantial weight gains in the boys with CF, but their weight declined rapidly after the prednisone was discontinued (Figure 2).

Prednisone also impaired growth in girls with CF during treatment. However, by age 18 these girls had reached heights and weights similar to those of the girls treated with placebo.

The researchers suspect that the different effects in boys and girls can be explained in part by the normal differences in time of entry into puberty. Dr. Lai said that prednisone given before puberty is thought to interfere with the activity of human growth hormone. Boys enter puberty later than girls, and CF is often associated with a further delay in puberty. The children in this study were 6 to 14 years old when they began taking prednisone. More of the girls would have already entered puberty and begun the normal growth spurt, so relatively fewer were in the vulnerable period.

"Physicians tend to think that after the corticosteroid is stopped, the patient will return to normal growth and make up for lost time," Dr. Lai said. "Don't make that assumption. If a child with CF has been taking prednisone for an extended time, monitor the patient's growth aggressively, and keep monitoring for the next few years."

--Janis Kelly

References
1. Lai HC, FitzSimmons SC, Allen DB, et al. Risk of persistent growth impairment after alternate-day prednisone treatment in children with cystic fibrosis. N Engl J Med. 2000;342:851-859.
2. Eigen H, Rosenstein BJ, FitzSimmons S, Schidlow DV, Cystic Fibrosis Foundation Prednisone Trial Group. A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis. J Pediatr. 1995;126:515-523.